The last 40 years have witnessed how p53 rose from a viral binding protein to a central factor in both stress responses and tumor suppression.The exquisite regulation of p53 functions is of vital importance for cell f...The last 40 years have witnessed how p53 rose from a viral binding protein to a central factor in both stress responses and tumor suppression.The exquisite regulation of p53 functions is of vital importance for cell fate decisions.Among the multiple layers of mechanisms controlling p53 function,posttranslational modifications (PTMs) represent an efficient and precise way.Major p53 PTMs include phosphorylation,ubiquitination,acetylation,and methylation.Meanwhile,other PTMs like sumoylation,neddylation,O-GlcNAcylation,adenosine diphosphate (ADP)-ribosylation,hydroxylation,and p-hydroxybutyrylation are also shown to play various roles in p53 regulation.By independent action or interaction,PTMs affect p53 stability,conformation,localization,and binding partners.Deregulation of the PTM-related pathway is among the major causes of p53-associated developmental disorders or diseases,especially in cancers.This review focuses on the roles of different p53 modification types and shows how these modifications are orchestrated to produce various outcomes by modulating p53 activities or targeted to treat different diseases caused by p53 dysregulation.展开更多
Chitosan,a deacetylated product of chitin,is a kind of natureal polysaccharide source which has shown important role in various areas.In this paper,in terms of cross test design we found the condition under which the ...Chitosan,a deacetylated product of chitin,is a kind of natureal polysaccharide source which has shown important role in various areas.In this paper,in terms of cross test design we found the condition under which the chitosan with high deacetylation can be obtained.The effects of preparing way and material shapes on deacetylation were investigated.In addition,we found the way for lowing hydrolysis of chitosan by putting small molecules,such as methyl alcohol,alcohol and acetone into acetic acid solution.展开更多
AIM To investigate the potential effect of curcumin on hepatitis B virus(HBV) covalently closed circular DNA(ccc DNA) and the underlying mechanism.METHODS A Hep G2.2.15 cell line stably transfected with HBV was treate...AIM To investigate the potential effect of curcumin on hepatitis B virus(HBV) covalently closed circular DNA(ccc DNA) and the underlying mechanism.METHODS A Hep G2.2.15 cell line stably transfected with HBV was treated with curcumin, and HBV surface antigen(HBs Ag) and e antigen(HBe Ag) expression levels were assessed by ELISA. Intracellular HBV DNA replication intermediates and ccc DNA were detected by Southern blot and real-time PCR, respectively. The acetylation levels of histones H3 and H4 were measured by Western blot. H3/H4-bound ccc DNA was detected by chromatin immunoprecipitation(Ch IP) assays. The deacetylase inhibitors trichostatin A and sodium butyrate were used to study the mechanism of action for curcumin. Additionally, short interfering RNAs(si RNAs) targeting HBV were tested along with curcumin.RESULTS Curcumin treatment led to time-and dose-dependent reductions in HBs Ag and HBe Ag expression and significant reductions in intracellular HBV DNA replication intermediates and HBV ccc DNA. After treatment with 20 μmol/L curcumin for 2 d, HBs Ag and ccc DNA levels in Hep G2.2.15 cells were reduced by up to 57.7%(P < 0.01) and 75.5%(P < 0.01), respectively, compared with levels in non-treated cells. Meanwhile, time-and dose-dependent reductions in the histone H3 acetylation levels were also detected upon treatment with curcumin, accompanied by reductions in H3-and H4-bound ccc DNA. Furthermore, the deacetylase inhibitors trichostatin A and sodium butyrate could block the effects of curcumin. Additionally, transfection of si RNAs targeting HBV enhanced the inhibitory effects of curcumin.CONCLUSION Curcumin inhibits HBV gene replication via downregulation of ccc DNA-bound histone acetylation and has the potential to be developed as a ccc DNA-targeting antiviral agent for hepatitis B.展开更多
Microglia play a pivotal role in clearance of Aβ by degrading them in lysosomes, countering amyloid pla- que pathogenesis in Alzheimer＇s disease （AD）. Recent evidence suggests that lysosomal dysfunction leads to i...Microglia play a pivotal role in clearance of Aβ by degrading them in lysosomes, countering amyloid pla- que pathogenesis in Alzheimer＇s disease （AD）. Recent evidence suggests that lysosomal dysfunction leads to insufficient elimination of toxic protein aggregates. We tested whether enhancing lysosomal function with transcription factor EB （TFEB）, an essential regulator modulating lysosomal pathways, would promote Aβ clearance in microglia. Here we show that microglial expression of TFEB facilitates fibrillar Aβ （fAβ） degra- dation and reduces deposited amyloid plaques, which are further enhanced by deacetylation of TFEB. Using mass spectrometry analysis, we firstly confirmed acetylation as a previously unreported modification of TFEB and found that SIRT1 directly interacted with and deacetylated TFEB at lysine residue 116. Subsequently, SIRT1 overexpression enhanced lysosomal function and fAβ degradation by upregulating transcriptional levels of TFEB downstream targets, which could be inhibited when TFEB was knocked down. Furthermore, overexpression of deacetylated TFEB at K116R mutant in microglia accelerated intracellular fAβ degradation by stimulating lysosomal biogenesis and greatly reduced the deposited amyloid plaques in the brain slices of APPIPS1 transgenic mice. Our findings reveal that deacetylaUon of TFEB could regulate lysosomal biogenesis and fAβ degradation, making microglial activation of TFEB a possible strategy for attenuating amyloid plaque deposition in AD.展开更多
The α-acetyl ketene dithioacetals 2, which bear various alkylthio groups, are a kind of important intermediates in organic synthesis. In this paper, dithioacetals 2 were prepared in very high yields (90%—100%) via t...The α-acetyl ketene dithioacetals 2, which bear various alkylthio groups, are a kind of important intermediates in organic synthesis. In this paper, dithioacetals 2 were prepared in very high yields (90%—100%) via the deacetylation reaction of the corresponding α,α-diacetyl ketene dithioacetals 1 in the presence of concentrated sulfuric acid. This reaction involves an %in-situ% electrophilic addition-deacetylation mechanism and shows the nucleophilicity of the α-carbon atom in α-oxo ketenedithioacetals. Meanwhile, when the reaction time was prolonged to 22—25 h, the β-keto thiolesters 3a and 3c were produced in good yields.展开更多
This paper presents experimental results on the effect of alkalis such as NaOH, KOH and Ca（OH）2 on deacetylation of a konjac glucomannan （KGM） powder under mechano-chemical （MC） treatment, The results show that ...This paper presents experimental results on the effect of alkalis such as NaOH, KOH and Ca（OH）2 on deacetylation of a konjac glucomannan （KGM） powder under mechano-chemical （MC） treatment, The results show that the alkalinity of modifiers is a dominant factor for deacetylation of KGM, In addition, characteristics, such as swelling property, viscous stability and thermal behavior of the deacetylated KGM are analyzed展开更多
文摘The last 40 years have witnessed how p53 rose from a viral binding protein to a central factor in both stress responses and tumor suppression.The exquisite regulation of p53 functions is of vital importance for cell fate decisions.Among the multiple layers of mechanisms controlling p53 function,posttranslational modifications (PTMs) represent an efficient and precise way.Major p53 PTMs include phosphorylation,ubiquitination,acetylation,and methylation.Meanwhile,other PTMs like sumoylation,neddylation,O-GlcNAcylation,adenosine diphosphate (ADP)-ribosylation,hydroxylation,and p-hydroxybutyrylation are also shown to play various roles in p53 regulation.By independent action or interaction,PTMs affect p53 stability,conformation,localization,and binding partners.Deregulation of the PTM-related pathway is among the major causes of p53-associated developmental disorders or diseases,especially in cancers.This review focuses on the roles of different p53 modification types and shows how these modifications are orchestrated to produce various outcomes by modulating p53 activities or targeted to treat different diseases caused by p53 dysregulation.
文摘Chitosan,a deacetylated product of chitin,is a kind of natureal polysaccharide source which has shown important role in various areas.In this paper,in terms of cross test design we found the condition under which the chitosan with high deacetylation can be obtained.The effects of preparing way and material shapes on deacetylation were investigated.In addition,we found the way for lowing hydrolysis of chitosan by putting small molecules,such as methyl alcohol,alcohol and acetone into acetic acid solution.
基金Supported by National Natural Science Foundation of China,No.81541140Natural Science Foundation of Hubei province of China,No.2014CFB645+2 种基金Research and Development project of the Science and Technology plan of Hubei province,No.2011BCB030Foundation for Innovative Research Teamof Hubei University of Medicine,No.2014CXG05Key program for precision Medicine of Taihe Hospital,No.2016JZ05
文摘AIM To investigate the potential effect of curcumin on hepatitis B virus(HBV) covalently closed circular DNA(ccc DNA) and the underlying mechanism.METHODS A Hep G2.2.15 cell line stably transfected with HBV was treated with curcumin, and HBV surface antigen(HBs Ag) and e antigen(HBe Ag) expression levels were assessed by ELISA. Intracellular HBV DNA replication intermediates and ccc DNA were detected by Southern blot and real-time PCR, respectively. The acetylation levels of histones H3 and H4 were measured by Western blot. H3/H4-bound ccc DNA was detected by chromatin immunoprecipitation(Ch IP) assays. The deacetylase inhibitors trichostatin A and sodium butyrate were used to study the mechanism of action for curcumin. Additionally, short interfering RNAs(si RNAs) targeting HBV were tested along with curcumin.RESULTS Curcumin treatment led to time-and dose-dependent reductions in HBs Ag and HBe Ag expression and significant reductions in intracellular HBV DNA replication intermediates and HBV ccc DNA. After treatment with 20 μmol/L curcumin for 2 d, HBs Ag and ccc DNA levels in Hep G2.2.15 cells were reduced by up to 57.7%(P < 0.01) and 75.5%(P < 0.01), respectively, compared with levels in non-treated cells. Meanwhile, time-and dose-dependent reductions in the histone H3 acetylation levels were also detected upon treatment with curcumin, accompanied by reductions in H3-and H4-bound ccc DNA. Furthermore, the deacetylase inhibitors trichostatin A and sodium butyrate could block the effects of curcumin. Additionally, transfection of si RNAs targeting HBV enhanced the inhibitory effects of curcumin.CONCLUSION Curcumin inhibits HBV gene replication via downregulation of ccc DNA-bound histone acetylation and has the potential to be developed as a ccc DNA-targeting antiviral agent for hepatitis B.
文摘Microglia play a pivotal role in clearance of Aβ by degrading them in lysosomes, countering amyloid pla- que pathogenesis in Alzheimer＇s disease （AD）. Recent evidence suggests that lysosomal dysfunction leads to insufficient elimination of toxic protein aggregates. We tested whether enhancing lysosomal function with transcription factor EB （TFEB）, an essential regulator modulating lysosomal pathways, would promote Aβ clearance in microglia. Here we show that microglial expression of TFEB facilitates fibrillar Aβ （fAβ） degra- dation and reduces deposited amyloid plaques, which are further enhanced by deacetylation of TFEB. Using mass spectrometry analysis, we firstly confirmed acetylation as a previously unreported modification of TFEB and found that SIRT1 directly interacted with and deacetylated TFEB at lysine residue 116. Subsequently, SIRT1 overexpression enhanced lysosomal function and fAβ degradation by upregulating transcriptional levels of TFEB downstream targets, which could be inhibited when TFEB was knocked down. Furthermore, overexpression of deacetylated TFEB at K116R mutant in microglia accelerated intracellular fAβ degradation by stimulating lysosomal biogenesis and greatly reduced the deposited amyloid plaques in the brain slices of APPIPS1 transgenic mice. Our findings reveal that deacetylaUon of TFEB could regulate lysosomal biogenesis and fAβ degradation, making microglial activation of TFEB a possible strategy for attenuating amyloid plaque deposition in AD.
文摘The α-acetyl ketene dithioacetals 2, which bear various alkylthio groups, are a kind of important intermediates in organic synthesis. In this paper, dithioacetals 2 were prepared in very high yields (90%—100%) via the deacetylation reaction of the corresponding α,α-diacetyl ketene dithioacetals 1 in the presence of concentrated sulfuric acid. This reaction involves an %in-situ% electrophilic addition-deacetylation mechanism and shows the nucleophilicity of the α-carbon atom in α-oxo ketenedithioacetals. Meanwhile, when the reaction time was prolonged to 22—25 h, the β-keto thiolesters 3a and 3c were produced in good yields.
文摘This paper presents experimental results on the effect of alkalis such as NaOH, KOH and Ca（OH）2 on deacetylation of a konjac glucomannan （KGM） powder under mechano-chemical （MC） treatment, The results show that the alkalinity of modifiers is a dominant factor for deacetylation of KGM, In addition, characteristics, such as swelling property, viscous stability and thermal behavior of the deacetylated KGM are analyzed
